Sodium valproate | Epilepsy clinician handbook
Sodium valproate is a good ‘all rounder’. Used first line in genetic generalised epilepsies (e.g. CAE, JAE, JME) and in refractory epilepsies such as Dravet Syndrome.
Avoid use in suspected mitochondrial disorders.
In the very young (<2 years old), consider the risk of hepatotoxicity. The aetiology of the neurological problem is helpful in deciding whether to use or not.
There are significant concerns regarding teratogenicity and all women of child bearing age must be alerted to this.
Important: Dosing information
Initiation and escalation doses on this webpage are a guide only.
All medications must be individualised based on:
- patient age, weight, co-morbidities
- disease, seizure type, frequency, duration
- medication metabolism, interactions, side-effect profile characteristics.
Further consultation with appropriate formularies or a paediatric neurologist may be required.
Dosing
Commonly used regime (without lamotrigine)
- Start 5mg/kg/day increasing weekly by 5-10mg/kg/day in two divided doses (depending upon the weight of child).
- Usual dose range is 10-30mg/kg/day.
- Dosages per kilogram can only be used up to weights of 30-40kgs.
- High doses of around 35mg/kg/day can be used with care and potential monitoring of platelets. At dosages above this, advice could be sought from a paediatric neurologist regarding efficacy and side-effect profile.
If the patient is on lamotrigine, please read: Lamotrigine and sodium valproate combination.
Preparations
- Syrup formulation is 40mg/ml – rounding to multiples of 40mg doses is convenient.
- Tablet 100mg - crushable
- Tablet Enteric Coated 200mg and 500mg.
Monitoring
- FBC and LFT - at baseline and 6-8 weeks after starting.
- Valproate levels can be measured but are variable and may not correlate to clinical efficacy – levels are done for a reason and not routinely measured.
Formulary
Possible side effects
- Appetite and weight gain (very common and can be intolerable).
Other notable side effects
- Thrombocytopenia (usually dose-related)
- Sedation
- Rash
- Dystonia/tremor (at higher doses)
- Pancreatitis
- Hepatotoxicity is idiosyncratic and those at most risk are children under the age of 2, metabolic aetiology, and/or multiple drugs, avoid in mitochondrial disorders
- There is some association with ovarian cysts.
- Rarely a picture of pseudodementia is described.
- For a complete list of adverse effects, appropriate formularies should be consulted.
Interactions and precautions
Valproate in pregnancy
- Sodium valproate has been associated with significant concerns of teratogenicity (i.e. malformations, cognitive impairment, and Autistic Spectrum Disorder).
- This is particularly true at higher dosages.
- The risk of teratogenicity increases with increasing dosage.
- It is important clinicians and women of child bearing age are aware of this risk.
- Ideally, pregnancies in women with epilepsy should be planned and managed by a neurologist.
- Medication choices should be selected and discussed keeping in mind the safety of mother and foetus.
- The Epilepsy Society Australia (ESA) has developed guidelines and position statements on certain clinical issues.
- The NICE Guideline on Epilepsies in children, young people and adults, was updated in April 2022 with advice regarding valproate use in women of childbearing age.
Monitoring
- FBC and LFT - at baseline and 6-8 weeks after starting.
- Valproate levels can be measured but are variable and may not correlate to clinical efficacy – levels are done for a reason and not routinely measured.
Resources
This information is reviewed annually by the Sydney Children’s Hospitals Network Paediatric Epilepsy NSW working group which includes medical, nursing, and pharmacy representation.